This invention relates to compositions for coating an implantable device or an endoluminal prosthesis, such as a stent. Moreover, the invention is directed to methods of coating a stent. The invention also relates to a biocompatible carrier containing an active agent for sustained release of the active agent to certain target cell populations, such as smooth muscle cells, requiring modulation to ameliorate a diseased state, particularly for the treatment of stenosis or restenosis following a vascular trauma or disease.
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially press against the atherosclerotic plaque of the lesion for remodeling of the vessel wall. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient""s vasculature.
A problem associated with the above procedure includes formation of intimal flaps or torn arterial linings which can collapse and occlude the conduit after the balloon is deflated. Vasospasms and recoil of the vessel wall also threaten vessel closure. Moreover, thrombosis and restenosis of the artery may develop over several months after the procedure, which may require another angioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, a stent is implanted in the lumen to maintain the vascular patency.
Stents are used not only as a mechanical intervention but also as a vehicle for providing biological therapy. As a mechanical intervention, stents act as scaffoldings, functioning to physically hold open and, if desired, to expand the wall of the passageway. Typically stents are capable of being compressed, so that they can be inserted through small cavities via catheters, and then expanded to a larger diameter once they are at the desired location. Examples in patent literature disclosing stents which have been successfully applied in PTCA procedures include stents illustrated in U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor. Mechanical intervention via stents has reduced the rate of restenosis as compared to balloon angioplasty; restenosis, however, is still a significant clinical problem. When restenosis does occur in the stented segment, its treatment can be challenging, as clinical options are more limited as compared to lesions that were treated solely with a balloon.
Biological therapy can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more favorable results.
A composition for coating a prosthesis such as a stent is provided. The composition comprises an amount of ethylene vinyl alcohol copolymer added to an amount of dimethyl acetamide solvent. The stent can be a radially expandable stent and can have a metallic body. The copolymer can constitute from about 0.1% to about 35% by weight of the total weight of the composition and the solvent can constitute from about 65% to about 99.9% by weight of the total weight of the composition.
In accordance with another embodiment, the composition can include an active agent such as actinomycin D, paclitaxel, docetaxel, or rapamycin. In this embodiment the copolymer can constitute about 0.1% to about 35%, the solvent about 50% to about 99.8%, and the active agent about 0.1% to about 40% by weight of the total weight of the composition.
In accordance with another embodiment, a co-solvent or a fluid can be added for increasing the dissolution of the active agent in the composition or for adjusting the wetting characteristic of the composition. The active agent can be added to the co-solvent prior to admixture with the composition. Suitable examples of the co-solvent can include, but are not limited to, propylene glycol methyl ether (PM), iso-propyl alcohol (IPA), n-propyl alcohol, methanol, ethanol, tetrahydrofuran (THF), dimethylformamide (DMF), and mixtures thereof.
In accordance with another aspect of the invention; a method of forming a composition to be applied to a stent is provided. The method comprises adding an amount of ethylene vinyl alcohol to an amount of dimethyl acetamide to form a composition used to form a coating for a stent. An active agent can also be added to the composition.
In accordance with another aspect of the invention, a method of coating a stent is provided comprising applying a composition to the stent; and blowing air onto the stent. The composition can include a polymer, such as ethylene vinyl alcohol copolymer, dissolved in a solvent, such as dimethyl acetamide. The composition can also include an active agent. The act of applying can be conducted by spraying the compositionat a flow rate of about 0.01 mg/second to about 1.0 mg/second. In accordance with one embodiment, the act of applying and blowing constitute a single cycle of coating application such that the method additionally includes repeating the cycle to form a coating of desirable weight or thickness. The act of applying the composition in a single cycle can be conducted from about 1 second to about 10 seconds. The act of blowing air in a single cycle can be conducted from about 3 seconds to about 60 seconds. About 0.1 micrograms to about 10 micrograms per cm of stent surface of coating can be deposited for each cycle. The blowing can be conducted at a temperature of about 30xc2x0 C. to about 60xc2x0 C. and at a flow rate of about 20 cubic feet/minute to about 80 cubic feet/minute. During the processing of the coating, the stent can be in an at least partially expanded state.